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Exopolysaccharide is detrimental for the symbiotic performance of Sinorhizobium fredii HH103 mutants with a truncated lipopolysaccharide core. 外多糖不利于具有截短脂多糖核心的裂殖单胞菌 HH103 突变体的共生性能。
IF 4.1 3区 生物学
Biochemical Journal Pub Date : 2024-10-25 DOI: 10.1042/bcj20240599
Francisco Fuentes-Romero,Marcello Mercogliano,Stefania De Chiara,Cynthia Alías-Villegas,Pilar Navarro-Gómez,Sebastián Acosta-Jurado,Alba Silipo,Carlos Medina,Miguel-Ángel Rodríguez-Carvajal,Marta S Dardanelli,José-Enrique Ruiz-Sainz,Francisco-Javier López-Baena,Antonio Molinaro,José-María Vinardell,Flaviana Di Lorenzo
{"title":"Exopolysaccharide is detrimental for the symbiotic performance of Sinorhizobium fredii HH103 mutants with a truncated lipopolysaccharide core.","authors":"Francisco Fuentes-Romero,Marcello Mercogliano,Stefania De Chiara,Cynthia Alías-Villegas,Pilar Navarro-Gómez,Sebastián Acosta-Jurado,Alba Silipo,Carlos Medina,Miguel-Ángel Rodríguez-Carvajal,Marta S Dardanelli,José-Enrique Ruiz-Sainz,Francisco-Javier López-Baena,Antonio Molinaro,José-María Vinardell,Flaviana Di Lorenzo","doi":"10.1042/bcj20240599","DOIUrl":"https://doi.org/10.1042/bcj20240599","url":null,"abstract":"The nitrogen-fixing rhizobia-legume symbiosis relies on a complex interchange of molecular signals between the two partners during the whole interaction. On the bacterial side, different surface polysaccharides, such as lipopolysaccharide (LPS) and exopolysaccharide (EPS), might play important roles for the success of the interaction. In a previous work we studied two Sinorhizobium fredii HH103 mutants affected in the rkpK and lpsL genes, which are responsible for the production of glucuronic acid and galacturonic acid, respectively. Both mutants produced an altered LPS, and the rkpK mutant, in addition, lacked EPS. These mutants were differently affected in symbiosis with Glycine max and Vigna unguiculata, with the lpsL mutant showing a stronger impairment than the rkpK mutant. In the present work we have further investigated the LPS structure and the symbiotic abilities of the HH103 lpsL and rkpK mutants. We demonstrate that both strains produce the same LPS, with a truncated core oligosaccharide devoid of uronic acids. We show that the symbiotic performance of the lpsL mutant with Macroptilium atropurpureum and Glycyrrhiza uralensis is worse than that of the rkpK mutant. Introduction of an exoA mutation (which avoids EPS production) in HH103 lpsL improved its symbiotic performance with G. max, M. atropurpureum, and G. uralensis to the level exhibited by HH103 rkpK, suggesting that the presence of EPS might hide the truncated LPS produced by the former mutant.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"5 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative Analysis of Canine and Human HtrA2 to Delineate Its Role in Apoptosis and Cancer. 比较分析犬和人的 HtrA2 以确定其在细胞凋亡和癌症中的作用
IF 4.1 3区 生物学
Biochemical Journal Pub Date : 2024-10-17 DOI: 10.1042/bcj20240295
Snehal Pandav Mudrale,Shubhankar Dutta,Kalyani Natu,Pradip Chaudhari,Kakoli Bose
{"title":"Comparative Analysis of Canine and Human HtrA2 to Delineate Its Role in Apoptosis and Cancer.","authors":"Snehal Pandav Mudrale,Shubhankar Dutta,Kalyani Natu,Pradip Chaudhari,Kakoli Bose","doi":"10.1042/bcj20240295","DOIUrl":"https://doi.org/10.1042/bcj20240295","url":null,"abstract":"Therapeutically, targeting the pro- and anti-apoptotic proteins has been one of the major approaches behind devising strategies to combat associated diseases. Human high-temperature requirement serine protease A2 (hHtrA2), which induces apoptosis through both caspase-dependent and independent pathways is implicated in several diseases including cancer, ischemic heart diseases, and neurodegeneration, thus making it a promising target molecule. In the recent past, the canine model has gained prominence in the understanding of human pathophysiology that was otherwise limited to the rodent system. Moreover, canine models in cancer research provide an opportunity to study spontaneous tumors as their size, lifespan, and environmental exposure are significantly closer to that of humans compared to laboratory rodents. Therefore, using HtrA2 as a model protein, comparative analysis has been done to revisit the hypothesis that canines might be excellent models for cancer research. We have performed evolutionary phylogenetic analyses that confirm a close relationship between canine and human HtrA2s. Molecular modeling demonstrates structural similarities including orientation of the catalytic triad residues, followed by in silico docking and molecular dynamics simulation studies that identify the potential interacting partners for canine HtrA2 (cHtrA2). In vitro biophysical and protease studies depict similarities in interaction with their respective substrates as well as transient transfection of cHtrA2 in mammalian cell culture shows induction of apoptosis. This work, therefore, promises to open a new avenue in cancer research through the study of spontaneous cancer model systems in canines.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"31 1","pages":""},"PeriodicalIF":4.1,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142447951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Filamin A regulates platelet shape change and contractile force generation via phosphorylation of the myosin light chain. 丝胶蛋白 A 通过肌球蛋白轻链的磷酸化调节血小板形状的改变和收缩力的产生。
IF 4.4 3区 生物学
Biochemical Journal Pub Date : 2024-10-17 DOI: 10.1042/BCJ20240114
Felix Hong, Molly Y Mollica, Kalyan Golla, Enoli De Silva, Nathan J Sniadecki, José A López, Hugh Kim
{"title":"Filamin A regulates platelet shape change and contractile force generation via phosphorylation of the myosin light chain.","authors":"Felix Hong, Molly Y Mollica, Kalyan Golla, Enoli De Silva, Nathan J Sniadecki, José A López, Hugh Kim","doi":"10.1042/BCJ20240114","DOIUrl":"10.1042/BCJ20240114","url":null,"abstract":"<p><p>Platelets are critical mediators of hemostasis and thrombosis. Platelets circulate as discs in their resting form but change shape rapidly upon activation by vascular damage and/or soluble agonists such as thrombin. Platelet shape change is driven by a dynamic remodeling of the actin cytoskeleton. Actin filaments interact with the protein myosin, which is phosphorylated on the myosin light chain (MLC) upon platelet activation. Actin-myosin interactions trigger contraction of the actin cytoskeleton, which drives platelet spreading and contractile force generation. Filamin A (FLNA) is an actin cross-linking protein that stabilizes the attachment between subcortical actin filaments and the cell membrane. In addition, FLNA binds multiple proteins and serves as a critical intracellular signaling scaffold. Here, we used platelets from mice with a megakaryocyte/platelet-specific deletion of FLNA to investigate the role of FLNA in regulating platelet shape change. Relative to controls, FLNA-null platelets exhibited defects in stress fiber formation, contractile force generation, and MLC phosphorylation in response to thrombin stimulation. Blockade of Rho kinase (ROCK) and protein kinase C (PKC) with the inhibitors Y27632 and bisindolylmaleimide (BIM), respectively, also attenuated MLC phosphorylation; our data further indicate that ROCK and PKC promote MLC phosphorylation through independent pathways. Notably, the activity of both ROCK and PKC was diminished in the FLNA-deficient platelets. We conclude that FLNA regulates thrombin-induced MLC phosphorylation and platelet contraction, in a ROCK- and PKC-dependent manner.</p>","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"1395-1410"},"PeriodicalIF":4.4,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Yop1 stability and membrane curvature generation propensity are controlled by its oligomerisation interface. Yop1 的稳定性和膜曲率生成倾向受其寡聚界面控制。
IF 4.4 3区 生物学
Biochemical Journal Pub Date : 2024-10-16 DOI: 10.1042/BCJ20240190
Anu V Chandran, Daniel Álvarez, Stefano Vanni, Jason R Schnell
{"title":"Yop1 stability and membrane curvature generation propensity are controlled by its oligomerisation interface.","authors":"Anu V Chandran, Daniel Álvarez, Stefano Vanni, Jason R Schnell","doi":"10.1042/BCJ20240190","DOIUrl":"10.1042/BCJ20240190","url":null,"abstract":"<p><p>The DP1 family of integral membrane proteins stabilize high membrane curvature in the endoplasmic reticulum and phagophores. Mutations in the human DP1 gene REEP1 are associated with Hereditary Spastic Paraplegia type 31 and distal hereditary motor neuropathy. Four missense mutations map to a putative dimerization interface but the impact of these mutations on DP1 structure and tubule formation are unknown. Combining biophysical measurements, functional assays, and computational modeling in the context of the model protein Yop1, we found that missense mutations have variable effects on DP1 dimer structure and in vitro tubulation activity, and provide mechanistic insights into the role of DP1 oligomerisation on membrane curvature stabilization. Whereas the mutations P71L and S75F decreased dimer homogeneity and led to polydisperse oligomerization and impaired membrane curving activity, A72E introduced new polar interactions between subunits that stabilized the Yop1 dimer and allowed robust tubule formation but prevented formation of more highly-curved lipoprotein particles (LPP). The introduction of a BRIL domain to the cytoplasmic loop of A72E rescued LPP formation, consistent with a requirement for dimer splaying in highly curved membranes. These results suggest that the membrane curving activity of DP1 proteins requires both dimer stability and conformational plasticity at the intermolecular interface.</p>","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"1437-1448"},"PeriodicalIF":4.4,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Adapting to change: resolving the dynamic and dual roles of NCK1 and NCK2. 适应变化:解决 NCK1 和 NCK2 的动态和双重作用。
IF 4.4 3区 生物学
Biochemical Journal Pub Date : 2024-10-16 DOI: 10.1042/BCJ20230232
Valentine Teyssier, Casey R Williamson, Erka Shata, Stephanie P Rosen, Nina Jones, Nicolas Bisson
{"title":"Adapting to change: resolving the dynamic and dual roles of NCK1 and NCK2.","authors":"Valentine Teyssier, Casey R Williamson, Erka Shata, Stephanie P Rosen, Nina Jones, Nicolas Bisson","doi":"10.1042/BCJ20230232","DOIUrl":"10.1042/BCJ20230232","url":null,"abstract":"<p><p>Adaptor proteins play central roles in the assembly of molecular complexes and co-ordinated activation of specific pathways. Through their modular domain structure, the NCK family of adaptor proteins (NCK1 and NCK2) link protein targets via their single SRC Homology (SH) 2 and three SH3 domains. Classically, their SH2 domain binds to phosphotyrosine motif-containing receptors (e.g. receptor tyrosine kinases), while their SH3 domains bind polyproline motif-containing cytoplasmic effectors. Due to these functions being established for both NCK1 and NCK2, their roles were inaccurately assumed to be redundant. However, in contrast with this previously held view, NCK1 and NCK2 now have a growing list of paralog-specific functions, which underscores the need to further explore their differences. Here we review current evidence detailing how these two paralogs are unique, including differences in their gene/protein regulation, binding partners and overall contributions to cellular functions. To help explain these contrasting characteristics, we then discuss SH2/SH3 structural features, disordered interdomain linker regions and post-translational modifications. Together, this review seeks to highlight the importance of distinguishing NCK1 and NCK2 in research and to pave the way for investigations into the origins of their interaction specificity.</p>","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"481 20","pages":"1411-1435"},"PeriodicalIF":4.4,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification of inhibitors of human ChaC1, a cytoplasmic glutathione degrading enzyme through high throughput screens in yeast. 通过酵母中的高通量筛选鉴定人ChaC1(一种细胞质谷胱甘肽降解酶)的抑制剂。
IF 4.1 3区 生物学
Biochemical Journal Pub Date : 2024-10-16 DOI: 10.1042/bcj20240447
Shradha Suyal,Chinmayee Choudhury,Deepinder Kaur,Anand K Bachhawat
{"title":"Identification of inhibitors of human ChaC1, a cytoplasmic glutathione degrading enzyme through high throughput screens in yeast.","authors":"Shradha Suyal,Chinmayee Choudhury,Deepinder Kaur,Anand K Bachhawat","doi":"10.1042/bcj20240447","DOIUrl":"https://doi.org/10.1042/bcj20240447","url":null,"abstract":"The cytosolic glutathione-degrading enzyme, ChaC1, is highly up-regulated in several cancers, with the up-regulation correlating to poor prognosis. The ability to inhibit ChaC1 is therefore important in different pathophysiological situations, but is challenging owing to the high substrate Km of the enzyme. As no inhibitors of ChaC1 are known, in this study we have focussed on this goal. We have initially taken a computational approach where a systemic structure-based virtual screening was performed. However, none of the predicted hits proved to be effective inhibitors. Synthetic substrate analogs were also not inhibitory. As both these approaches targeted the active site, we shifted to developing two high-throughput, robust, yeast-based assays that were active site independent. A small molecule compound library was screened using an automated liquid handling system using these screens. The hits were further analyzed using in vitro assays. Among them, juglone, a naturally occurring naphthoquinone, completely inhibited ChaC1 activity with an IC50 of 8.7 µM. It was also effective against the ChaC2 enzyme. Kinetic studies indicated that the inhibition was not competitive with the substrate. Juglone is known to form adducts with glutathione and is also known to selectively inhibit enzymes by covalently binding to active site cysteine residues. However, juglone continued to inhibit a cysteine-free ChaC1 variant, indicating that it was acting through a novel mechanism. We evaluated different inhibitory mechanisms, and also analogues of juglone, and found plumbagin effective as an inhibitor. These compounds are the first inhibitor leads against the ChaC enzymes using a robust yeast screen.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"10 1","pages":"1475-1495"},"PeriodicalIF":4.1,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142436178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CDS2 expression regulates de novo phosphatidic acid synthesis. CDS2 的表达调控 PA 的从头合成。
IF 4.4 3区 生物学
Biochemical Journal Pub Date : 2024-10-16 DOI: 10.1042/BCJ20240456
Daniel M Collins, Vishnu Janardan, David Barneda, Karen E Anderson, Izabella Niewczas, Diane Taylor, Danye Qiu, Henning J Jessen, Andrea F Lopez-Clavijo, Simon Walker, Padinjat Raghu, Jonathan Clark, Len R Stephens, Phillip T Hawkins
{"title":"CDS2 expression regulates de novo phosphatidic acid synthesis.","authors":"Daniel M Collins, Vishnu Janardan, David Barneda, Karen E Anderson, Izabella Niewczas, Diane Taylor, Danye Qiu, Henning J Jessen, Andrea F Lopez-Clavijo, Simon Walker, Padinjat Raghu, Jonathan Clark, Len R Stephens, Phillip T Hawkins","doi":"10.1042/BCJ20240456","DOIUrl":"10.1042/BCJ20240456","url":null,"abstract":"<p><p>CDS enzymes (CDS1 and 2 in mammals) convert phosphatidic acid (PA) to CDP-DG, an essential intermediate in the de novo synthesis of PI. Genetic deletion of CDS2 in primary mouse macrophages resulted in only modest changes in the steady-state levels of major phospholipid species, including PI, but substantial increases in several species of PA, CDP-DG, DG and TG. Stable isotope labelling experiments employing both 13C6- and 13C6D7-glucose revealed loss of CDS2 resulted in a minimal reduction in the rate of de novo PI synthesis but a substantial increase in the rate of de novo PA synthesis from G3P, derived from DHAP via glycolysis. This increased synthesis of PA provides a potential explanation for normal basal PI synthesis in the face of reduced CDS capacity (via increased provision of substrate to CDS1) and increased synthesis of DG and TG (via increased provision of substrate to LIPINs). However, under conditions of sustained GPCR-stimulation of PLC, CDS2-deficient macrophages were unable to maintain enhanced rates of PI synthesis via the 'PI cycle', leading to a substantial loss of PI. CDS2-deficient macrophages also exhibited significant defects in calcium homeostasis which were unrelated to the activation of PLC and thus probably an indirect effect of increased basal PA. These experiments reveal that an important homeostatic response in mammalian cells to a reduction in CDS capacity is increased de novo synthesis of PA, likely related to maintaining normal levels of PI, and provides a new interpretation of previous work describing pleiotropic effects of CDS2 deletion on lipid metabolism/signalling.</p>","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"1449-1473"},"PeriodicalIF":4.4,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11555650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Permeation mechanisms of hydrogen peroxide and water through Plasma Membrane Intrinsic Protein aquaporins. 过氧化氢和水通过质膜固有蛋白(PIP)水蒸发蛋白的渗透机制。
IF 4.4 3区 生物学
Biochemical Journal Pub Date : 2024-10-02 DOI: 10.1042/BCJ20240310
Jonathan Chevriau, Gerardo Zerbetto De Palma, Cintia Jozefkowicz, Victoria Vitali, Agustina Canessa Fortuna, Nicolas Ayub, Gabriela Soto, Gerd Patrick Bienert, Ari Zeida, Karina Alleva
{"title":"Permeation mechanisms of hydrogen peroxide and water through Plasma Membrane Intrinsic Protein aquaporins.","authors":"Jonathan Chevriau, Gerardo Zerbetto De Palma, Cintia Jozefkowicz, Victoria Vitali, Agustina Canessa Fortuna, Nicolas Ayub, Gabriela Soto, Gerd Patrick Bienert, Ari Zeida, Karina Alleva","doi":"10.1042/BCJ20240310","DOIUrl":"10.1042/BCJ20240310","url":null,"abstract":"<p><p>Hydrogen peroxide (H2O2) transport by aquaporins (AQP) is a critical feature for cellular redox signaling. However, the H2O2 permeation mechanism through these channels remains poorly understood. Through functional assays, two Plasma membrane Intrinsic Protein (PIP) AQP from Medicago truncatula, MtPIP2;2 and MtPIP2;3 have been identified as pH-gated channels capable of facilitating the permeation of both water (H2O) and H2O2. Employing a combination of unbiased and enhanced sampling molecular dynamics simulations, we investigated the key barriers and translocation mechanisms governing H2O2 permeation through these AQP in both open and closed conformational states. Our findings reveal that both H2O and H2O2 encounter their primary permeation barrier within the selectivity filter (SF) region of MtPIP2;3. In addition to the SF barrier, a second energetic barrier at the NPA (asparagine-proline-alanine) region that is more restrictive for the passage of H2O2 than for H2O, was found. This behavior can be attributed to a dissimilar geometric arrangement and hydrogen bonding profile between both molecules in this area. Collectively, these findings suggest mechanistic heterogeneity in H2O and H2O2 permeation through PIPs.</p>","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":" ","pages":"1329-1347"},"PeriodicalIF":4.4,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Advances in the cell biology of the trafficking and processing of amyloid precursor protein: impact of familial Alzheimer's disease mutations. 淀粉样前体蛋白贩运和处理的细胞生物学研究进展:家族性阿尔茨海默病突变的影响。
IF 4.1 3区 生物学
Biochemical Journal Pub Date : 2024-10-02 DOI: 10.1042/bcj20240056
Jingqi Wang,Lou Fourriere,Paul A Gleeson
{"title":"Advances in the cell biology of the trafficking and processing of amyloid precursor protein: impact of familial Alzheimer's disease mutations.","authors":"Jingqi Wang,Lou Fourriere,Paul A Gleeson","doi":"10.1042/bcj20240056","DOIUrl":"https://doi.org/10.1042/bcj20240056","url":null,"abstract":"The production of neurotoxic amyloid-β peptides (Aβ) is central to the initiation and progression of Alzheimer's disease (AD) and involves sequential cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. APP and the secretases are transmembrane proteins and their co-localisation in the same membrane-bound sub-compartment is necessary for APP cleavage. The intracellular trafficking of APP and the β-secretase, BACE1, is critical in regulating APP processing and Aβ production and has been studied in several cellular systems. Here, we summarise the intracellular distribution and transport of APP and its secretases, and the intracellular location for APP cleavage in non-polarised cells and neuronal models. In addition, we review recent advances on the potential impact of familial AD mutations on APP trafficking and processing. This is critical information in understanding the molecular mechanisms of AD progression and in supporting the development of novel strategies for clinical treatment.","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"14 1","pages":"1297-1325"},"PeriodicalIF":4.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Retraction: Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies. 撤回:手机频率电磁场短期激活ERK的机制
IF 4.1 3区 生物学
Biochemical Journal Pub Date : 2024-10-02 DOI: 10.1042/bj20061653_ret
{"title":"Retraction: Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies.","authors":"","doi":"10.1042/bj20061653_ret","DOIUrl":"https://doi.org/10.1042/bj20061653_ret","url":null,"abstract":"","PeriodicalId":8825,"journal":{"name":"Biochemical Journal","volume":"27 1","pages":"1327"},"PeriodicalIF":4.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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